K. C. Murdock, et al., J. Med. Chem., 22, 1024 (1979) have recently synthesized a group of 1,4-bis[(aminoalkyl)amino]anthraquinones which show anti-cancer activity in warm-blooded animals. Further investigation of some of these compounds indicates that they bind to deoxyribonucleic acid (DNA) by sandwiching between successive pairs of the nucleic acid bases of DNA [Johnson, et al., Cancer Treatment Reports, 63, 425 (1979)]. This type of insertion-binding of certain flat, polycyclic aromatic molecules to DNA is called intercalation and is also characteristic of some other drugs [Schwartz, Biomedicine, 24, 317 (1976)].
While the mechanism of action of the compounds described in the J. Med. Chem. reference vide supra, as well as the compounds of the current invention has not been verified, it is the inventors expectation that an anthraquinone nucleus with suitable basic side chains may intercalate into the DNA of cancer cells and thereby block their proliferation, and further, that two such anthraquinone systems, connected by suitable linking units, may intercalte into two positions of the same DNA chain, thereby enabling binding with greater strength and permanence. Alternatively, such double binding or bis-intercalation may link the adjacent strands of normally double stranded DNA and thereby prevent the separation of the strands, which is known to be required for DNA replication and cellular proliferation. Proliferation may also be impaired if one or both ends of such doubled anthraquinones are bound to other cellular components such as cell membranes, mitochondria, phospholipids or proteins.
While a biochemical mode of action has not been established, the following invention describes a series of bis-anthraquinones which substantially increase the life span of cancerous mice.